scholarly journals Effects of lycopene on the induction of foam cell formation by modified LDL

2007 ◽  
Vol 293 (6) ◽  
pp. E1820-E1827 ◽  
Author(s):  
Mariarosaria Napolitano ◽  
Clara De Pascale ◽  
Caroline Wheeler-Jones ◽  
Kathleen M. Botham ◽  
Elena Bravo
Keyword(s):  
Foam Cell ◽  
Scavenger Receptor ◽  
Cell Formation ◽  
Lipid Synthesis ◽  
Receptor Activity ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell ◽  
Modified Ldl ◽  
Tnf Α ◽  
Anti Inflammatory

The effect of lycopene on macrophage foam cell formation induced by modified low-density lipoprotein (LDL) was studied. Human monocyte-derived macrophages (HMDM) were incubated with lycopene in the presence or absence of native LDL (nLDL) or LDL modified by oxidation (oxLDL), aggregation (aggLDL), or acetylation (acLDL). The cholesterol content, lipid synthesis, scavenger receptor activity, and the secretion of inflammatory [interleukin (IL)-1β and tumor necrosis factor (TNF)-α] and anti-inflammatory (IL-10) cytokines was determined. Lycopene was found to decrease the synthesis of cholesterol ester in incubations without LDL or with oxLDL while triacylglycerol synthesis was reduced in the presence of oxLDL and aggLDL. Scavenger receptor activity as assessed by the uptake of acLDL was decreased by ∼30% by lycopene. In addition, lycopene inhibited IL-10 secretion by up to 74% regardless of the presence of nLDL or aggLDL but did not affect IL-1β or TNF-α release. Lycopene also reduced the relative abundance of mRNA transcripts for scavenger receptor A (SR-A) in THP-1 macrophages treated with aggLDL. These findings suggest that lycopene may reduce macrophage foam cell formation induced by modified LDL by decreasing lipid synthesis and downregulating the activity and expression of SR-A. However, these effects are accompanied by impaired secretion of the anti-inflammatory cytokine IL-10, suggesting that lycopene may also exert a concomitant proinflammatory effect.

scholarly journals TRAIL/DR5 Signaling Promotes Macrophage Foam Cell Formation by Modulating Scavenger Receptor Expression

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e87059 ◽  
Author(s):  
Fang Fang Liu ◽  
Xiao Wu ◽  
Yun Zhang ◽  
Yan Wang ◽  
Fan Jiang
Keyword(s):  
Foam Cell ◽  
Scavenger Receptor ◽  
Cell Formation ◽  
Receptor Expression ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell

Abstract 333: CD36 Mediates Cholesterol Uptake via Na/K-ATPase/lyn Signaling in Macrophages

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Yiliang Chen ◽  
David Kennedy ◽  
Zhichuan Li ◽  
Zijian Xie ◽  
Roy L Silverstein
Keyword(s):  
Kinase Activity ◽  
Foam Cell ◽  
Oxidized Ldl ◽  
Scavenger Receptor ◽  
Cell Formation ◽  
Developed Countries ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell ◽  
Cholesterol Uptake ◽  
Lyn Kinase

Atherosclerosis, the leading cause of death in the developed countries, is characterized by macrophage foam cell formation. We previously showed that CD36, a scavenger receptor highly expressed in macrophages, mediates oxidized-LDL uptake, contributes to intracellular cholesterol accumulation and foam cell formation, and regulates macrophage migration and pro-inflammatory signaling. Consistently, cd36 deletion in mice protects from diet-induced atherosclerosis. Mechanistically, we discovered a novel signaling pathway, in which oxidized LDL (oxLDL) binding to CD36 activates Lyn kinase and initiates a cascade that is necessary for the pro-atherogenic cellular phenotype. How CD36 regulates Lyn kinase remains undefined. Since we previously showed that the Na/K-ATPase (NKA) regulates Src family kinases, including Lyn, we hypothesized that CD36 regulates Lyn kinase via an interaction with NKA. We used co-immunoprecipitation, FRET, and a novel cross linking assay to demonstrate that CD36 physically associates with NKA on the macrophage surface. Using a Lyn kinase activity assay, we showed that the interaction regulates Lyn kinase activity in response to oxLDL in macrophages. Moreover, a newly developed peptide inhibitor specifically blocked Lyn activation in response to oxLDL and attenuated oxLDL-stimulated cholesterol uptake (135.6±3.4 μM cholesterol/mg protein after 24 hours vs 173.8±7.7 μM cholesterol/mg protein in vehicle treated cells; p=0.0005; n=6). Taken together, we conclude that CD36 signals through NKA to regulate Lyn kinase activity in macrophages, which may be a molecular mechanism underlying cholesterol overloading and foam cell formation.

β-Amyloid (Aβ40, Aβ42) binding to modified LDL accelerates macrophage foam cell formation

2007 ◽  
Vol 1771 (10) ◽  
pp. 1335-1344 ◽  
Author(s):  
Berta Schulz ◽  
Gerhard Liebisch ◽  
Margot Grandl ◽  
Tobias Werner ◽  
Stefan Barlage ◽  
...  
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell ◽  
Modified Ldl ◽  
Β Amyloid

scholarly journals Chondroitin Sulfate N -acetylgalactosaminyltransferase-2 Impacts Foam Cell Formation and Atherosclerosis by Altering Macrophage Glycosaminoglycan Chain

2021 ◽  
Vol 41 (3) ◽  
pp. 1076-1091
Author(s):  
Imam Manggalya Adhikara ◽  
Keiko Yagi ◽  
Dyah Samti Mayasari ◽  
Yoko Suzuki ◽  
Koji Ikeda ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Foam Cell ◽  
Oxidized Ldl ◽  
Scavenger Receptor ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Peritoneal Macrophages ◽  
Metabolic Phenotype ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell

Objective: Chondroitin sulfate proteoglycans are the primary constituents of the macrophage glycosaminoglycan and extracellular microenvironment. To examine their potential role in atherogenesis, we investigated the biological importance of one of the chondroitin sulfate glycosaminoglycan biosynthesis gene, ChGn-2 (chondroitin sulfate N -acetylgalactosaminyltransferase-2), in macrophage foam cell formation. Approach and Results: ChGn-2-deficient mice showed decreased and shortened glycosaminoglycans. ChGn-2 −/− /LDLr −/− (low-density lipoprotein receptor) mice generated less atherosclerotic plaque after being fed with Western diet despite exhibiting a metabolic phenotype similar to that of the ChGn-2 +/+ /LDLr −/− littermates. We demonstrated that in macrophages, ChGn-2 expression was upregulated in the presence of oxLDL (oxidized LDL), and glycosaminoglycan was substantially increased. Foam cell formation was significantly altered by ChGn-2 in both mouse peritoneal macrophages and the RAW264.7 macrophage cell line. Mechanistically, ChGn-2 enhanced oxLDL binding on the cell surface, and as a consequence, CD36—an important macrophage membrane scavenger receptor—was differentially regulated. Conclusions: ChGn-2 alteration on macrophages conceivably influences LDL accumulation and subsequently accelerates plaque formation. These results collectively suggest that ChGn-2 is a novel therapeutic target amenable to clinical translation in the future. Graphic Abstract: A graphic abstract is available for this article.

Chemerin-9, a potent agonist of chemerin receptor (ChemR23), prevents atherogenesis

2019 ◽  
Vol 133 (16) ◽  
pp. 1779-1796 ◽  
Author(s):  
Kengo Sato ◽  
Hayami Yoshizawa ◽  
Tomomi Seki ◽  
Remina Shirai ◽  
Tomoyuki Yamashita ◽  
...  
Keyword(s):  
Coronary Arteries ◽  
Foam Cell ◽  
Umbilical Vein ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell ◽  
Tnf Α ◽  
Atheromatous Plaques

Abstract Plasma levels of chemerin, an adipocytokine produced from the adipose tissues and liver, are associated with metabolic syndrome and coronary artery disease (CAD). Chemerin and its analog, chemerin-9, are known to bind to their receptor, ChemR23. However, whether chemerin and chemerin-9 affect atherogenesis remains to be elucidated. We investigated the expression of chemerin and ChemR23 in human coronary arteries and cultured human vascular cells. The effects of chemerin and chemerin-9 on atheroprone phenomena were assessed in human THP1 monocytes, human umbilical vein endothelial cells (HUVECs), and human aortic smooth muscle cells (HASMCs) and aortic lesions in Apoe−/− mice. In patients with CAD, a small amount of ChemR23, but not chemerin, was expressed within atheromatous plaques in coronary arteries. Chemerin and ChemR23 were expressed at high levels in THP1 monocytes, THP1-derived macrophages, and HUVECs; however, their expression in HASMCs was weak. Chemerin and chemerin-9 significantly suppressed the tumor necrosis factor-α (TNF-α)-induced mRNA expression of adhesion and pro-inflammatory molecules in HUVECs. Chemerin and chemerin-9 significantly attenuated the TNF-α-induced adhesion of THP1 monocytes to HUVECs and macrophage inflammatory phenotype. Chemerin and chemerin-9 suppressed oxidized low-density lipoprotein (oxLDL)-induced macrophage foam cell formation associated with down-regulation of CD36 and up-regulation of ATP-binding cassette transporter A1 (ABCA1). In HASMCs, chemerin and chemerin-9 significantly suppressed migration and proliferation without inducing apoptosis. In the Apoe−/− mice, a 4-week infusion of chemerin-9 significantly decreased the areas of aortic atherosclerotic lesions by reducing intraplaque macrophage and SMC contents. Our results indicate that chemerin-9 prevents atherosclerosis. Therefore, the development of chemerin analogs/ChemR23 agonists may serve as a novel therapeutic target for atherosclerotic diseases.

scholarly journals Blockade of Macrophage CD147 Protects Against Foam Cell Formation in Atherosclerosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Jian-Jun Lv ◽  
Hao Wang ◽  
Hong-Yong Cui ◽  
Ze-Kun Liu ◽  
Ren-Yu Zhang ◽  
...  
Keyword(s):  
Foam Cell ◽  
Scavenger Receptor ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell ◽  
Atherosclerotic Lesions ◽  
Cd147 Expression ◽  
Compound Screening ◽  
Genetic Deletion ◽  
Atherosclerosis Development

The persistence of macrophage-derived foam cells in the artery wall fuels atherosclerosis development. However, the mechanism of foam cell formation regulation remains elusive. We are committed to determining the role that CD147 might play in macrophage foam cell formation during atherosclerosis. In this study, we found that CD147 expression was primarily increased in mouse and human atherosclerotic lesions that were rich in macrophages and could be upregulated by ox-LDL. High-throughput compound screening indicated that ox-LDL-induced CD147 upregulation in macrophages was achieved through PI3K/Akt/mTOR signaling. Genetic deletion of macrophage CD147 protected against foam cell formation by impeding cholesterol uptake, probably through the scavenger receptor CD36. The opposite effect was observed in primary macrophages isolated from macrophage-specific CD147-overexpressing mice. Moreover, bioinformatics results indicated that CD147 suppression might exert an atheroprotective effect via various processes, such as cholesterol biosynthetic and metabolic processes, LDL and plasma lipoprotein clearance, and decreased platelet aggregation and collagen degradation. Our findings identify CD147 as a potential target for prevention and treatment of atherosclerosis in the future.

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